Breast tumors display remarkable biological and clinical heterogeneity as covered extensively in the Introduction and Progress Report. Developing a better understanding of the molecular basis of such heterogeneity is central to the goal of rational, individualized treatment for patients based on molecular profiling. A large number of pathways, including RTKs, RAF/MEK/ERK, AKT, NFKB, JAK/STAT, JNK, p38, etc. work to control diverse cellular processes. In cancer the aberrant activity of the system is responsible for proliferation, apoptosis and other hallmarks of cancer. Diverse open questions concerning both the basic biology of cancer signaling and related therapeutic implications are rooted in tumor-specific network connectivity. The need to elucidate such tumor specific connectivity motivates the broad goals of this project.